• 대한한방내과학회지
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• 제20권1호
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• pp.133-142
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• 1999

To clarifiy the effects of Scolopendrae corpus(S-C) on turmor promotion in two-stage carcinogenesis in mice was investigated. In vivo system, S-C were seen to gave an inhibitory activity on TPA-induced mouse ear edema. In addition, the S-C were proved to have antitumor-promoting activity in two-stage mouse skin carcinogenesis induced by DMBA and two-stage mouse lung carcinogenesis induced by 4-NQO as a initiator plus TPA and glycerol as a promoter. Moreover, S-C significantly exhibited an cytolytic effect in $HepG_2$ cells and showed significant antitumor activity against Sarcoma-180 bearing mice by oral administration. These results suggest that S-C could be effective in adjuvant chemotherapy for human cancer.

• BMB Reports
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• 제38권3호
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• pp.300-306
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• 2005

Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast cancer. It showed a degree of hepatic carcinogenesis, when it used for long term as it can decrease the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in liver rat cells leading to liver injury. In this study, a model of liver injury in female rats was done by intraperitoneal injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days. This model produced a state of oxidative stress accompanied with liver injury as noticed by significant declines in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of 200 mg/kg body weight daily for 10 successive days, resulted in alleviation of the oxidative stress status of tamoxifen-intoxicated liver injury in rats as observed by significant increments in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases; sGPT and sGOT levels. The administration of DDB before tamoxifen intoxication (as protection) is more little effective than its curative effect against tamoxifen-induced liver injury. The data obtained from this study speculated that DDB can mediate its biochemical effects through the enhancement of the antioxidant enzyme activities and reduced glutathione level as well as decreasing lipid peroxides.

• Molecules and Cells
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• 제42권1호
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• pp.87-95
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• 2019

Long interspersed element-1 (LINE-1 or L1) is an autonomous retrotransposon, which is capable of inserting into a new region of genome. Previous studies have reported that these elements lead to genomic variations and altered functions by affecting gene expression and genetic networks. Mounting evidence strongly indicates that genetic diseases or various cancers can occur as a result of retrotransposition events that involve L1s. Therefore, the development of methodologies to study the structural variations and interpersonal insertion polymorphisms by L1 element-associated changes in an individual genome is invaluable. In this study, we applied a systematic approach to identify human-specific L1s (i.e., L1Hs) through the bioinformatics analysis of high-throughput next-generation sequencing data. We identified 525 candidates that could be inferred to carry non-reference L1Hs in a Korean individual genome (KPGP9). Among them, we randomly selected 40 candidates and validated that approximately 92.5% of non-reference L1Hs were inserted into a KPGP9 genome. In addition, unlike conventional methods, our relatively simple and expedited approach was highly reproducible in confirming the L1 insertions. Taken together, our findings strongly support that the identification of non-reference L1Hs by our novel target enrichment method demonstrates its future application to genomic variation studies on the risk of cancer and genetic disorders.

• Toxicological Research
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• 제35권2호
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• pp.131-136
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• 2019

Ethylhexyl dimethyl para-aminobenzoic acid (PABA) is an oily yellow liquid derivative of water-soluble PABA commonly used in sunscreen. Ethylhexyl dimethyl PABA is widely used as an ingredient in many cosmetics at an average concentration of 1.25% (0.5-2.0%) in Korea. Previous studies, including those involving animals, have demonstrated that ethylhexyl dimethyl PABA is toxic to the following four organs: testis, epididymis, spleen, and liver. In addition, experiments using human keratinocytes found that ethylhexyl dimethyl PABA inhibits cell growth and DNA synthesis at low concentrations, and halted the cell cycle of MM96L cells (human melanoma cell line) at the G1 phase. Despite limited clinical data in humans, many studies have confirmed increased mutagenicity of ethylhexyl dimethyl PABA following exposure to sunlight, which suggests that this molecule is likely to contribute to onset of sun-induced cancer despite protecting the skin through absorption of UVB. For risk assessment, the no observed adverse effect level (NOAEL) chosen was 100 mg/kg bw/day in a 4 weeks oral toxicity study. Systemic exposure dosage (SED) was 0.588 mg/kg bw/day for maximum use of ethylhexyl dimethyl PABA in cosmetics. Based on the risk assessment and exposure scenarios conducted in this study, the margin of safety (MOS) was calculated to be 180.18 for a sunscreen containing 8% ethylhexyl dimethyl PABA, which is the maximum level allowed by the relevant domestic authorities.

• 동의생리병리학회지
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• 제32권4호
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• pp.261-270
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• 2018

The aim of this study was to evaluate the antitumor activities of Typhae pollen (TP) by confirming in vitro cytotoxicity and in vivo anti-tumor and immune-modulatory effect with anti-cachexia effect. The MTT assay is used in HepG2 cell to detect potential cytotoxic activities of aqueous extract of Typhae pollen (TPe). After HepG2 tumor cell implantation, eight mice per groups were assigned to six groups. Three different dosages of TPe (500, 250 and 125 mg/kg) were orally administered in the amount of $10m{\ell}/kg$ and sorafenib also administered 20mg/kg, every day for 35 days from 28 days after the tumor cell implantation. We observed the changes on body weights, tumor volume and weights, lymphatic organ, serum interferon $(IFN)-{\gamma}$ levels, splenocytes and peritoneal NK cell activity, splenic tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, IL-10 contents. Periovarian fat weights, serum IL-6 levels, thicknesses of deposited periovarian adipose tissue and mean diameters were also detected to monitor the tumor-related anticachexic effects. In tumor masses, the immunoreactivities of cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (cleaved PARP) - apoptotic marks, cyclooxygenase-2 (COX-2), inducible nitric oxide synthases (iNOS) and tumor necrosis factor $(TNF)-{\alpha}$ were additionally observed by immunohistochemistry. The results were compared with sorafenib. Decreases of COX-2 were demonstrated in sorafenib and TPe treated mice and also increases of iNOS in tumor masses were observed in TPe, not in sorafenib. TPe increased periovarian fat pad weights compared with tumor-bearing controls and sorafenib treated mice. TPe showed increases of splenic $TNF-{\alpha}$, IL-10 and $IL-1{\beta}$, serum $IFN-{\gamma}$ and NK cell activities corresponding to increases of spleen weights, lymph node weights and non-atrophic changes of lymph nodes. Our results show oral treatment of TPe 500, 250 and 125 mg/kg has potent in vitro and in vivo antitumor activities through modest cytotoxic effects, immunomodulatory effects and apoptotic activities in HepG2 tumor cells. In addition, TPe can prevent cancer related cachexia.

• Asian Pacific Journal of Cancer Prevention
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• 제15권8호
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• pp.3495-3501
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• 2014

Melanoma-associated antigen (MAGE) family genes have been considered as potentially promising targets for anticancer immunotherapy. MAGED4 was originally identified as a glioma-specific antigen. Current knowledge about MAGED4 expression in glioma is only based on mRNA analysis and MAGED4 protein expression has not been elucidated. In the present study, we investigated this point and found that MAGED4 mRNA and protein were absent or very lowly expressed in various normal tissues and glioma cell line SHG44, but overexpressed in glioma cell lines A172,U251,U87-MG as well as glioma tissues, with significant heterogeneity. Furthermore, MAGED4 protein expression was positively correlated with the glioma type and grade. We also found that the expression of MAGED4 inversely correlated with the overall methylation status of the MAGED4 promoter CpG island. Furthermore, when SHG44 and A172 with higher methylation were treated with the DNA demethylating agent 5-aza-2'-deoxycytidine (5-AZA-CdR) reactivation of MAGED4 mRNA was mediated by significant demethylation in SHG44 instead of A172. However, 5-AZA-CdR treatment had no effect on MAGED4 protein in both SHG44 and A172 cells. In conclusion, MAGED4 is frequently and highly expressed in glioma and is partly regulated by DNA methylation. The results suggest that MAGED4 might be a promising target for glioma immunotherapy combined with 5-AZA-CdR to enhance its expression and eliminate intratumor heterogeneity.

• 한국식품과학회지
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• 제36권1호
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• pp.141-146
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• 2004

여러 발표에서 버섯추출물의 간접적 항종양효과에 대해 보고 되고 있다. 본 연구는 표고버섯의 직접적인 종양세포주 성장억제효과를 탐지하기 위하여 휴먼자궁경부암바이러스 타입 16의 종양유전자가 발현된 동물종양세포주(TC-1)를 이용하였다. 여러 추출용매 중 물을 이용한 추출액에서 TC-1 세포주의 성장억제효과를 탐지할 수 있었다. 이들 세포성장저해는 추출물첨가농도에 상응하며 $IC_{50}$는 $800\;{\mu}g/mL$로 계산되었다. 또한, 표고버섯 물 추출물은 휴먼자궁경부암세포주(CaSki and HeLa)에서도 유사한 세포성장억제효과를 보여 주었다. 첨가농도가 1.5 mg/mL에서는 첨가후 6시간째에 벌써 완전한 종양세포주(TC-1)의 성장억제가 탐지되었다. 이들 추출물을 열처리시 종양세포주성장억제가 소실되었으나 pH의 변화에서는 그대로 종양세포주성장억제효과가 탐지되었다. 이는 표고버섯 물 추출물 내에 있는 항종양물질이 열에 민감함을 의미한다. Annexin V 및 propidium iodide 염색에 의해 이들 TC-1종양세포주의 성장 억제효과는 apoptosis에 의해 매개됨을 보여 주었다 동물실험에서 표고버섯 물 추출물의 구강투여시 TC-1유래 종양의 성장 및 생성에 아무 효과를 주지 못하였다. 반면, 형성된 종양에 직접 주사시 종양크기의 감소가 탐지되었다. 요약하면 이들 연구에서 표고버섯 물 추출물에 존재하는 항암물질은 열에 민감하며 apoptosis에 의해 휴먼자궁경부암종양유전자에 의해 종양화된 세포주의 세포성장을 직접 억제하는 기능이 있음을 증명한다.

• 한국식품위생안전성학회지
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• 제28권4호
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• pp.360-366
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• 2013

본 연구는 Spragye-Dawely 계통의 암컷 랫드에서 종합비타민의 반복경구투여 독성평가와 대식세포 Raw 264.7 세포의 NO 및 TNF-${\alpha}$ assay를 통한 면역 활성을 평가하기 위해서 실시하였다. 종합비타민을 대식세포의 활성능을 측정하기 위해 Raw 264.7 세포에서 NO와 TNF-${\alpha}$의 생성을 측정하였다. 종합비타민을 대식세포에 24시간 처리한 결과 대조군과 비교 시 NO와 TNF-${\alpha}$가 유의적으로 상승하였다. 이 결과 종합비타민이 대식세포인 Raw 264.7 세포를 활성화시키는 것으로 사료된다. 또한 랫드에서 종합비타민의 독성평가를 위하여 랫드에 종합비타민을 0.24 g/kg, 1 g/kg 그리고 2 g/kg을 4주 동안 경구투여를 하였다. 종합비타민의 안전성을 확인하기 위해 다음과 같은 관찰 및 검사를 하였다. 검사항목으로는 체중과 사료 섭취량, 임상증상, 혈청생화학적 검사를 관찰한 결과 대조군과 투여군을 비교 시 유의적인 변화가 나타나지 않았다. 따라서 종합비타민은 생리대사에 무해하며 면역증강의 효과를 나타내는 것으로 사료된다.

• 대한수의학회지
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• 제52권2호
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• pp.125-131
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• 2012

Rabbit hemorrhagic disease is a highly acute and fatal viral disease caused by rabbit hemorrhagic disease virus (RHDV). Since first outbreak in Korea 1987, RHDV has been continually affected in the country, but the pattern of outbreak seem to be changed. In this study, to understand the pathogenesis of the new RHDVa serotype, we therefore carried out to inoculate RHDVa to rabbits, and to examine the sequential histopathologic changes and viral distribution. Macroscopically, various sized dark red or white spots or appearance were observed in the liver, lung, kidney uterus and ureter. In euhanized rabbits, significant pathologic findings such as infiltration of heterophils and mononuclear cells were observed at 24 hours after inoculation (HAI), and these were sequentially extended periportal to centrilobular area. However, in dead rabbits, severe hepatic degeneration and/or necrosis with relatively weak inflammatory responses were observed. RHDV antigens began to detect in liver, spleen, and lung from 12 HAI by PCR. Immunohistochemically, RHDV positive cells were seen in only liver from 24 HAI, and the degree of immunogen reactivity was stronger in dead rabbits than in euthanized ones. In conclusion, RHDVa caused the subacute or chronic infection accompanying low mortality and moderate to severe inflammatory reaction in rabbits, suggesting the possibility that RHD could become endemic.

• 동의생리병리학회지
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• 제21권4호
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• pp.856-859
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• 2007

We have investigated the antimetastatic and antitumor effects of Ginsenoside Rh2 and ${\beta}-glucan$ unsing an experimental metastatic mouse model intravenously injected with B 16 melanoma F 10 cells. Animal groups are divided into six groups according to the dosage of drug administration and the kind of drugs. The groups are control, ${\beta}-glucan$ with 50, 100 and 200 mg/kg, Geinsenoside Rh2 50 mg/kg, and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg. Oral administration of various concentration of ${\beta}-glucan$( 50, 100, and 200 mg/kg) were reduced the lung- metastatics induced by metastatic B16 melanoma F 10 cells injection with a dose dependent manner in the syngenic mice. At same dosage group, Ginsenoside Rh2 (50 mg/kg) has more antimetastatic effect than the ${\beta}-glucan$(50 mg/kg). The highest antimetastatic effects was observed in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group and has a similar tendency in the anti-tumor effects, including decrease of the average tumor weight and increase of the average survival rate. There are no differences of the average tumor weights were apparent in the ${\beta}-glucan$ groups, however there were little decrease of the average tumor weight in Ginsenoside 50 mg/kg group and ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group than that of the control group. The rate of average survival rate in the ${\beta}-glucan$ 50 mg/kg + Ginsenoside Rh2 50 mg/kg group, ${\beta}-glucan$ 200 mg/kg, ${\beta}-glucan$ 100 mg/kg and ${\beta}-glucan$ 50 mg/kg, and Ginsenoside 50 mg/kg groups were highly in order. These data suggest that antimetastatic and antitumor effect of combination of Ginsenodide Rh2 and ${\beta}-glucan$ be the highest in this study.